Long-Term Exposure to Nitrogen Dioxide and Ozone and Mortality: Update of the WHO Air Quality Guidelines Systematic Review and Meta-Analysis.

Objectives: We performed a systematic review and meta-analysis on long-term exposure to nitrogen dioxide (NO₂) and ozone (O₃) with mortality, to expand evidence that informed 2021 the WHO Air Quality Guidelines and guide the Health Risks of Air Pollution in Europe project.

Methods: We included cohorts investigating NO₂ and O₃ mortality from all-causes, respiratory diseases, chronic obstructive pulmonary disease (COPD), acute lower respiratory infections (ALRI); and NO₂ mortality from circulatory, ischemic heart, cerebrovascular diseases and lung cancer. We pooled estimates by random-effects models and investigated heterogeneity. We assessed the certainty of the evidence using the Grading of Recommendations Assessment Development approach and Evaluation (GRADE).

Results: We selected 83 studies for NO₂ and 26 for O₃ for the meta-analysis. NO₂ was associated with all outcomes, except for cerebrovascular mortality. O₃ was associated with respiratory mortality following annual exposure. There was high heterogeneity, partly explained by region and pollutant levels. Certainty was high for NO₂ with COPD and ALRI, and annual O₃ with respiratory mortality.

Conclusion: An increasing body of evidence, with new results from countrywide areas and the Western Pacific, supports certainty, including new outcomes.